HSV-1 Infection Accelerates the Progression of Alzheimer’s Disease: Through the Regulation of Microglial Phagocytosis and Activation of the NLRP3 Pathway

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Research Background

With the intensification of global aging, Alzheimer’s Disease (AD) has become a neurodegenerative disease affecting millions of people. In recent years, an increasing number of studies have suggested that Herpes Simplex Virus Type 1 (HSV-1) may be related to the development and progression of Alzheimer’s Disease. HSV-1 infection can induce the deposition of β-Amyloid (Aβ), but its exact role and mechanism are still unclear. Against this background, this study aims to explore the impact of HSV-1 infection on AD and its related mechanisms.

Study Source

This study was initiated by Zhimeng Wang and others from the School of Medicine at Tsinghua University, Beijing, and the State Key Laboratory of Stem Cells and Reproductive Biology, Chinese Academy of Sciences, among other institutions. The research results were published in the Journal of Neuroinflammation in 2024, with the DOI link being: 10.1186/s12974-024-03166-9.

Research Details

Subjects and Methods

This study selected transgenic 5xFAD mice as the research model, which were infected with the HSV-1-GFP virus. The study focused on the impact of HSV-1 infection on Aβ deposition, microglial phagocytic activity, and cognitive function. Various techniques such as immunofluorescence staining, Western blot, behavioral testing, flow cytometry, and real-time quantitative PCR were used for comprehensive analysis. A small molecule drug, MCC950 sodium, was used as a selective inhibitor of the NLRP3 inflammasome pathway for intervention experiments.

Main Results

The experiment showed that HSV-1 infection significantly accelerated the deposition and aggregation of Aβ in the brains of transgenic mice and caused a significant decline in cognitive function. The study further revealed the crucial role of the NLRP3 inflammasome signaling pathway in the HSV-1-induced Aβ deposition and the AD process. Inhibition of the NLRP3 inflammasome signaling with MCC950 sodium significantly reduced Aβ deposition and slowed cognitive decline.

Research Conclusions and Significance

The study results support that HSV-1 infection is an important etiological factor in AD and clarify the function of NLRP3 inflammasome activation at the interface of HSV-1 infection and Aβ deposition. The study provides new insights into the connection between HSV-1 infection and AD and offers a scientific basis for developing new therapies against AD triggered by HSV-1 infection.

Research Highlights

• Defined the phenomenon that HSV-1 infection accelerates the progression of Alzheimer’s Disease.
• Discovered the regulatory role of the NLRP3 inflammasome in HSV-1 infection-induced Aβ deposition.
• Proposed NLRP3 inflammasome inhibitors as a potential strategy for treating AD.

Additional Information

This study not only provides new insights into the connection between HSV-1 and AD but also reveals the complex role played by microglia in neuroinflammation and neurodegenerative diseases. The in-depth research helps to understand the mechanism of AD development and paves the way for finding new treatment schemes.